Orthopedic and Rehabilitation Engineering
Effects of Prehabilitation Exercise on Segmental Defect Bone Healing
Lia Strait, BE
PhD Student
University of Oregon
Eugene, Oregon, United States
Kylie Williams
PhD Candidate Bioengineering
University of Oregon, Knight Campus for Accelerating Scientific Impact, United States
Dayne Dewan
Undergraduate Research Assistant
University of Oregon, United States
Tyler Guyer
PhD Candidate
University of Oregon, United States
Nick Willett, PhD
Associate Professor
University of Oregon, Knight Campus, United States
Robert Guldberg
Executive Director
University of Oregon, Knight Campus for Accelerating Scientific Impact, United States
Exercise can help maintain healthy musculoskeletal tissue1 and regulate inflammation2. The inflammatory response is a known, critical mediator of fracture healing3, however little is known about how frequent exercise affects the inflammatory response to fracture, and subsequent bone healing. Fractures remain a considerable clinical burden, with each American expected to experience two fractures in their lifetime4.
Studies have shown exercise to increase bone volume and cortical thickness5, therefore this study sought to elucidate if regular exercise prior to surgery would alter bone morphological properties before injury. Further, whether pre-surgical exercise would modulate inflammation and improve bone healing in a femoral defect model. We hypothesized that 4-weeks of prehabilitative treadmill running before surgery would increase bone volume, bone mineral density and functional properties, as well as decrease systemic inflammation. We further hypothesized animals exercising prior to fracture would show improved overall healing after injury as compared to sedentary controls.
To investigate the effects of frequent exercise on bone healing, 9-week-old female Wistar rats (n=8) were pretrained for two weeks running on a treadmill with a 5° incline. Following the pre-training period, rats prehabed for 2-weeks running 5days/week for 30min/day at 18m/min with a 5° incline. These running conditions placed their exertion level at ~70-75% VO2 max. Sedentary controls (n=8) were brought into the treadmill room each day to control for stress. At days 0 and 28, blood was drawn for systemic immune profiling (data pending) and bone morphology was characterized via Micro-CT scans. Post-prehabilitation, we created a 2mm femoral defect stabilized with internal fixation. All subjects remained sedentary post-surgery. Blood was drawn at days 3 and 7 after surgery, and every two weeks following. Bone properties and healing were assessed via in vivo x-ray and Micro-CT scans every two weeks. Longitudinal bone properties were analyzed using a two-way ANOVA with repeated measures (p< 0.05). All data are displayed as mean ± sem.
Contrary to our hypothesis, the prehab group had a significantly lower bone volume (p=0.0452) than sedentary animals after prebilitation and prior to surgery. Prehab animals also had significantly lower mechanical properties, as indicated by both the proximal and distal polar moment of inertia, than their sedentary counterparts. Changes in the mechanical properties and morphology of bone in response to treadmill running are inconsistent in the literature5. However, weight-bearing exercise in general has been shown to increase bone volume, density and cortical thickness6. We hypothesize that our results are due to the adolescent age of the rats at the start of exercise as previous literature has found exercise to impact adolescent skeletal development7.
Despite this, bone volume in the exercise group 4 weeks post-fracture (1.336 mm3) was 2X that observed in the sedentary group (0.6602 mm3), although the difference was not significant at this early timepoint. Further, early callus formation was only observed in the prehabilitated animals at 4-weeks. Our pending systemic immune profiling may elucidate the mechanisms behind our exercise-induced improved bone healing. This study is ongoing but preliminary results suggest routine exercise prior to fracture may expedite bone healing and reduce non-union rates.
1. Distefano, G. & Goodpaster, B. H. Effects of Exercise and Aging on Skeletal Muscle. Cold Spring Harb. Perspect. Med. 8, a029785 (2018).
2. Scheffer, D. da L. & Latini, A. Exercise-induced immune system response: Anti-inflammatory status on peripheral and central organs. Biochim. Biophys. Acta Mol. Basis Dis. 1866, 165823 (2020).
3. Baht, G. S., Vi, L. & Alman, B. A. The Role of the Immune Cells in Fracture Healing. Curr. Osteoporos. Rep. 16, 138–145 (2018).
4. Arm Injury Statistics | Aids for One Armed Tasks. https://u.osu.edu/productdesigngroup3/sample-page/.
5. Portier, H., Benaitreau, D. & Pallu, S. Does Physical Exercise Always Improve Bone Quality in Rats? Life 10, 217 (2020).
6. Hong, A. R. & Kim, S. W. Effects of Resistance Exercise on Bone Health. Endocrinol. Metab. 33, 435–444 (2018).
7. Bourrin, S., Genty, C., Palle, S., Gharib, C. & Alexandre, C. Adverse effects of strenuous exercise: a densitometric and histomorphometric study in the rat. J. Appl. Physiol. Bethesda Md 1985 76, 1999–2005 (1994).